From the Gene to the Genome

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From the Gene to the Genome

• Genetic Inheritance Patterns
• Observing Genetic Differences in the DNA

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Each human has 46 chromosomes. Each parent
provides one member of a matched (homologous)
chromosome pair.
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Chromosomal Locations of Genes

• Locus area on chromosome where gene is located
  
• Paired chromosomes have genes in the same order,
  but may have different forms of a gene at the
  same locus
• Alleles alternative forms of a gene
• Dominant allele masks other alleles
• Recessive allele is masked
• Gene sequence of DNA that codes for a protein,
  gives rise to physical trait

Locus 1
Locus 2
Locus 3
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Separation ofChromosome Pairs
recessive allele
dominant allele
Each sex cell will carry only one allele for
each gene
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Inheritance Pattern for One Gene(for genes on
pairs 1-22)
TT or Tt no disease tt Tay-Sachs disease
Donald, no disease
Darla, no disease
Tt
Tt
Tt
Chances with each pregnancy 75 no disease25
Tay-Sachs disease
TT
Tt
tt
homozygous recessive
homozygous dominant
heterozygous(carrier)
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Molecular Basis for Effects of Dominant and
Recessive Alleles

• Dominant Allele
• codes for a functional protein
• eg. T allele gives instructions for making
  Hexosaminidase A (Hex A), an enzyme involved in
  lipid metabolism
• Recessive Allele
• codes for a non-functional protein or prevents
  any protein product from being formed
• eg. with the t allele, no functional Hex A is
  detected

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Variations in Genetic Patterns Codominance
Neither allele masks the other so that effects of
both alleles are observed in heterozygotes
without blending
Example ABO Blood Type
Alleles A and B are codominant. Alleles A and B
are completely dominant over o.
Effects of both alleles observed in phenotype
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Variations in Genetic Patterns Multiple Alleles
Three or more alleles exist for one traitNote
A person can only carry any two of
these alleles at once.
Examples ABO Blood Typeand also Rh Factor
Although there are multiple R alleles, R1, R2,
R3, etc. all are completely dominant over all of
the r alleles, r1, r2, r3, etc.
ABO Blood Type and Rh Factor are controlled by
separate genes. They are inherited
independently.
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Variations in Genetic Patterns Polygenic
Inheritance
Many genes affect one trait Example Skin color
Based on a study conducted in Jamaica.
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Variations in Genetic Patterns Sex Influenced
Genes
Genes that have different dominance patterns in
males and females
Example Pattern BaldnessCaused by a dominant
allele in males,but a recessive allele in females
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Inheritance for Sex-linked Genes(for genes on
pair 23)
Males carry only one copy of genes on the X
chromosomeFemales can be homozygous or
heterozygous these genes
GrampsXhY
Hemophilic Male Non-hemophilic
Female
(father is hemophilic)
x XHXh
XhY
H no hemophiliah hemophilia
XH Xh
XHXh
XhXh
Xh Y
XHY
XhY
Chance for each pregnancy ¼ non-hemophilic
females ¼ hemophilic females ¼ non-hemophilic
males ¼ hemophilic males
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The Human Genome Project Genetic Differences at
the DNA Level
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Studying DNA

• Cut chromosomal DNA into smaller pieces with
  restriction enzymes

5 A A G T C G G A T C C T G A C G T 3 3
T T C A G C C T A G G A C T G C A 5
G A T C C T G A C G T 3 G A C T G
C A 5
5 A A G T C G 3 T T C A G C C T A G
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Studying DNA

• Cut chromosomal DNA into smaller pieces with
  restriction enzymes
• Separate DNA pieces by size using agarose gel
  electrophoresis

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(No Transcript)
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Agarose Gel Electrophoresis
larger fragments
smaller fragments
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Studying DNA

• Transfer DNA to filter for analysis with probe
  that will bind to specific sequence

DNA pattern on filter will be identical to gel
separation pattern.
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Studying DNA

• Probe sequence of DNA that is complementary
  to the sequence of interest Used to locate a
  copy of the DNA sequence by hybridization

Denature DNA by heating
Add Probe Probe Binds to gene
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DNA Pattern on Gel Pattern on Filter
after probe
binding
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Studying DNA

• Allow probe to bind to DNA on filter, visualize
  region of probe attachment

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Studying DNA

• Identify similarities and differences between
  individuals Paternity Testing

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Studying DNA

• Identify patterns that are unique to specific
  genes Medical Genetic Testing

On the basis of this analysis, the genotype of
the fetus is 1. AS 2. AA 3. SS
4. Unknown
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Future Directions Gene Therapy
Andrew Gobea
Treated for SCID Severe Combined Immune
Deficiency
Ashanthi DeSilva